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| Verfasst von: | Demircan, Muhammed Burak [VerfasserIn]  |
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| | Zinser, Luca J. [VerfasserIn] |
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| | Michels, Alexander [VerfasserIn] |
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| | Guaza-Lasheras, Mar [VerfasserIn] |
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| | John, Fabian [VerfasserIn] |
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| | Gorol, Johanna M. [VerfasserIn] |
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| | Theuerkauf, Samuel [VerfasserIn] |
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| | Günther, Dorothee M. [VerfasserIn] |
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| | Grimm, Dirk [VerfasserIn] |
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| | Greten, Florian [VerfasserIn] |
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| | Chlanda, Petr [VerfasserIn] |
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| | Thalheimer, Frederic [VerfasserIn] |
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| | Buchholz, Christian J. [VerfasserIn] |
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| Titel: | T-cell specific in vivo gene delivery with DART-AAVs targeted to CD8 |
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| Verf.angabe: | Muhammed Burak Demircan, Luca J. Zinser, Alexander Michels, Mar Guaza-Lasheras, Fabian John, Johanna M. Gorol, Samuel A. Theuerkauf, Dorothee M. Günther, Dirk Grimm, Florian R. Greten, Petr Chlanda, Frederic B. Thalheimer, and Christian J. Buchholz |
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| E-Jahr: | 2024 |
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| Jahr: | 2 October 2024 |
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| Umfang: | 15 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Online verfügbar: 08. August 2024 ; Gesehen am 04.04.2025 |
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| Titel Quelle: | Enthalten in: Molecular therapy |
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| Ort Quelle: | Amsterdam : Elsevier, 2000 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 32(2024), 10, Seite 3470-3484 |
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| ISSN Quelle: | 1525-0024 |
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| Abstract: | One of the biggest challenges for in vivo gene therapy are vectors mediating highly selective gene transfer into a defined population of therapy-relevant cells. Here we present DARPin-targeted AAVs (DART-AAVs) displaying DARPins specific for human and murine CD8. Insertion of DARPins into the GH2/GH3 loop of the capsid protein 1 (VP1) of AAV2 and AAV6 resulted in high selectivity for CD8-positive T cells with unimpaired gene delivery activity. Remarkably, the capsid core structure was unaltered with protruding DARPins detectable. In complex primary cell mixtures, including donor blood or systemic injections into mice, the CD8-targeted AAVs were by far superior to unmodified AAV2 and AAV6 in terms of selectivity, target cell viability, and gene transfer rates. In vivo, up to 80% of activated CD8+ T cells were hit upon a single vector injection into conditioned humanized or immunocompetent mice. While gene transfer rates decreased significantly under non-activated conditions, genomic modification selectively in CD8+ T cells was still detectable upon Cre delivery into indicator mice. In both mouse models, selectivity for CD8+ T cells was close to absolute with exceptional detargeting from liver. The CD8-AAVs described here expand strategies for immunological research and in vivo gene therapy options. |
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| DOI: | doi:10.1016/j.ymthe.2024.08.002 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1016/j.ymthe.2024.08.002 |
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| | kostenfrei: Volltext: https://www.sciencedirect.com/science/article/pii/S1525001624005240 |
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| | DOI: https://doi.org/10.1016/j.ymthe.2024.08.002 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | AAV capsid engineering |
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| | CD8 targeting |
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| | CD8-AAV |
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| | DART-AAVs |
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| | delivery |
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| | gene therapy |
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| | receptor targeting |
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| | T cell activation |
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| | T cell targeting |
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| | targeted AAV |
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| | targeted gene therapy |
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| | viral vectors |
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| K10plus-PPN: | 1921600578 |
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| Verknüpfungen: | → Zeitschrift |
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T-cell specific in vivo gene delivery with DART-AAVs targeted to CD8 / Demircan, Muhammed Burak [VerfasserIn]; 2 October 2024 (Online-Ressource)
